Tubular cell HIV-entry through apoptosed CD4 T cells: A novel pathway

Priyanka Singh, Hersh Goel, Mohammad Husain, Xiqian Lan, Joanna Mikulak, Ashwani Malthotra, Saul Teichberg, Helena Schmidtmayerova, Pravin C. Singhal

Research output: Contribution to journalArticle

Abstract

We hypothesized that HIV-1 may enter tubular cells by phagocytosis of apoptotic fragments of HIV-1-infected T cells infiltrating tubular interstitium. The study was designed to evaluate the interaction of programmed death-1 (PD-1) receptors on CD4 T cells and programmed death ligand-1 (PD-L1) on tubular cells (HK2 and HRPTEC, primary tubular cells). Co-cultivation of HIV-1 infected lymphocytes (HIV-LY) with HK2s/HRPTECs resulted in T cell apoptosis, uptake of the apoptosed HIV-LY by HK2s/HRPTECs, tubular cell activation and HIV expression. Cytochalasin-B inhibited tubular cell HIV-LY uptake and anti-PD-L1 antibody inhibited HIV-LY apoptosis and tubular cell HIV-LY uptake, activation and HIV expression. These observations do indicate induction of apoptosis of T cells due to interaction of PD-1 and PD-L1 upon co-cultivation and subsequent phygocytosis of HIV-laden apoptotic bodies by tubular cells and thus the transfer of HIV-1 into tubular cells. These findings identify a novel pathway that facilitates HIV-1 entry into tubular cell.

Original languageEnglish
Pages (from-to)68-77
Number of pages10
JournalVirology
Volume434
Issue number1
DOIs
Publication statusPublished - Dec 5 2012

    Fingerprint

Keywords

  • Apoptosis
  • HIV
  • Human proximal tubular cells
  • PD-1 receptor
  • PD-L1
  • Phagocytosis
  • Reactive oxygen species
  • T cell

ASJC Scopus subject areas

  • Virology

Cite this

Singh, P., Goel, H., Husain, M., Lan, X., Mikulak, J., Malthotra, A., Teichberg, S., Schmidtmayerova, H., & Singhal, P. C. (2012). Tubular cell HIV-entry through apoptosed CD4 T cells: A novel pathway. Virology, 434(1), 68-77. https://doi.org/10.1016/j.virol.2012.09.009